Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer's Disease

Abstract

Background: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer's disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia.

Objective: To unravel mutual and divergent functional alterations in Alzheimer's disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer's disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17).

Methods: In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series from 66 regions for correlation analysis.

Results: Apart from differing connections between Alzheimer's disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes.

Conclusion: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain's functional disconnectivity in Alzheimer's disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures.

Keywords: Alzheimer’s disease; functional connectivity; semantic dementia; temporal lobe.

Fig.1

Areas with significantly lower (voxel-level) gray matter (GM) density (top) and effect size in terms of percentage GM reduction (bottom) in (A) the semantic dementia (SD) patients (n = 24) and (B) Alzheimer’s disease (AD) patients (n = 18) compared to the healthy elderly control group (n = 20). SD patients showed reduced GM density in widespread areas of the left anterior temporal cortex including the temporal pole, while the AD patients showed reduced GM density in the amygdala. SD patients showed more severe GM loss with up to 70% reduction, and AD patients with up to 40% reduction in some areas.

Fig.2

Z-scores of seven connections (edges 1–7) with significant group differences. Post-hoc tests between the three groups were performed, and significant group differences are denoted with gray horizontal lines (see Table 2 for a detailed description of the ROIs). Ring-shaped circles represent single subject data points. Filled circles represent outliers.

Fig.3

Functional connectivity (FC) strengths of the three groups. Color shades and thickness of the links are proportional to FC strengths; shades of red reflect positive, shades of blue negative strengths. Numbers in HC group indicate edge numbers (see Table 2 for a detailed description of the ROIs). ROIs in the left hemisphere are labeled yellow, ROIs in the right hemisphere labeled green.